This K23 application is submitted by Michael A. Dimyan, MD, Assistant Professor of Neurology at the University Of Maryland School Of Medicine. My long-term goal is to become an independent clinical investigator focusing on the neural substrates of arm motor control as a basis for developing interventions to improve neurorehabilitation after stroke. This K23 award will allow me to pursue advanced training in arm motor control and their neurophysiological substrates. I will train in the technique of concurrent multimodal neurophysiology and imaging. This training will be applied to investigating the dynamic modulation of interhemispheric inhibition throughout the time-course of arm activity, with a goal of identifying targets for intervention to enhance arm rehabilitation after stroke. I will be mentored by a team of experts in clinical neurorehabilitation, arm motor control, neurophysiology and multi-modal imaging including Dr. George Wittenberg, Dr. Jill Whitall, Dr. Rao Gullapalli and Dr. Peter Gorman. Even after comprehensive rehabilitation, 30% of stroke survivors are left with arm weakness. Chronic hemiparesis is significant because 50% of the reduction in quality of life for stroke survivors is due to arm weakness. Current treatments of hemiparesis are based on different models of how the two arms interact after stroke. However, these models are limited by an incomplete understanding of interhemispheric competition. In particular, we do not know how interactions between the two arms are dynamically modulated during arm activity. I will pursue this problem by 1) defining normal interhemispheric interactions between the two arms during unilateral arm activity 2) discovering how aging and stroke impair those dynamics and 3) determining how other brain areas influence the interaction between the two arms. This will be done by studying neurophysiological measures of corticospinal and interhemispheric interactions in hemiparetic patients and healthy controls performing an arm activity. I will also use multimodal neurophysiological and imaging techniques to examine brain network interactions and their influence on corticospinal activity. The proposed research is innovative conceptually in its elaboration and addition to the model of interhemispheric interactions during movement and after stroke. The results of this research may significantly contribute to our understanding of the interaction between the two arms. This is important because it will allow us to design therapies that take advantage of those interactions. The impact of this proposal is that it will allow us to design interventions that taret specific neurophysiological impairments at specific time-points during movement to enhance rehabilitation after stroke. This research proposal addresses the NIH missions to reduce the burden of neurological disorders and enhance the quality of life of people with disabilities. This proposal also addresses the goals of the NIH BRAIN initiative to develop a dynamic picture of the human brain describing how neural circuits interact in time and space.